The History and Future of Clinical Genetics Research Part 2)

Tuesday 30 August 2011

Ruth Burton – Product Manager Genomic Solutions

Clinical genetics research today

Today, the use of cytogenetics is prevalent in the research approaches to identifying congenital disorders, as well as diseases where genetic changes have a strong influence, such as cancer. This includes traditional karyotyping using FISH and other staining methods, as well as molecular approaches such as aCGH (Figure 1). For example, the detection of cancer aberrations is an area that incorporates all of the approaches available to the modern clinical researcher. aCGH is becoming a powerful tool for assessing the genomic mutations present in cancer samples, and has the potential to replace traditional research methods by providing increased accuracy and speed of interpretation. However, in those cases where the malignant tissue is composed of a complex mosaic of cells exhibiting multiple different genetic lesions, aCGH is often combined with karyotyping and FISH to accurately characterise the variations defining the malignant cell population.

Another area where microarrays are replacing traditional research techniques is during prenatal screening for genetic abnormalities, mostly due to their high resolution. Typically, foetal genomic DNA is screened using aCGH so that genetic diseases can be detected early during pregnancy. In a similar way, aCGH may offer the ability to improve the success of in vitro fertilisation (IVF). Known as Pre-implantation Genetic Screening (PGS), the technique involves using aCGH to assess the genetic status of IVF embryos before they are transferred for implantation into the mother. The chances of IVF success are often limited by the chromosomal quality of the eggs provided by the mother. As the age of the mother increases, the chance of harvesting eggs with genomic aberrations also increases, while in other cases the mother may be affected by a known genetic abnormality that might influence IVF success. By screening each embryo using aCGH, it is possible to select only those embryos that are likely to make it to full term and lead to the birth of a healthy child, maximising the success IVF.

As molecular approaches continue to impact on the work carried out in clinical research laboratories, the standards in place to ensure the highest possible data quality, and therefore data accuracy, must be continually updated. For example, the American College of Medical Genetics, formed in 1991 to help improve health through medical genetics, regularly publishes a list of internationally-recognised standards and guidelines describing best practices for testing using genetic approaches. In addition, the International Standards for Cytogenomic Arrays (ISCA) Consortium, of which OGT is a member, is a growing group of molecular genetics laboratories actively working towards improving healthcare through the establishment of guidelines for molecular testing, including the creation of standardised aCGH arrays for clinical genetics research. The Cancer Cytogenomics Microarray Consortium (CCMC) is a similar group, recently founded with the goal of maximising the benefits provided by microarrays for cancer research. These groups continue to work towards outlining a set of standards to ensure that molecular techniques improve and enhance the services provided by clinical research laboratories.